[Federal Register Volume 78, Number 48 (Tuesday, March 12, 2013)]
[Proposed Rules]
[Pages 15660-15664]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-05577]
=======================================================================
-----------------------------------------------------------------------
CONSUMER PRODUCT SAFETY COMMISSION
[CPSC Docket No. CPSC-2013-0010]
16 CFR Part 1500
Hazardous Substances and Articles; Supplemental Definition of
``Strong Sensitizer''
AGENCY: Consumer Product Safety Commission.
ACTION: Notice of proposed rulemaking.
-----------------------------------------------------------------------
SUMMARY: The U.S. Consumer Product Safety Commission (CPSC or
Commission) proposes to update the supplemental definition of ``strong
sensitizer'' under the Federal Hazardous Substances Act (FHSA). The
proposed amendment clarifies or adds language to eliminate redundancy,
remove certain subjective factors, incorporate new and anticipated
technology, rank the criteria for classification of strong sensitizers
in order of importance, define criteria for ``severity of reaction,''
and indicate that a weight-of-evidence approach will be used to
determine the strength of the sensitizer.
DATES: Written comments must be received by May 28, 2013.
ADDRESSES: You may submit comments identified by Docket No. CPSC-2013-
0010, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov. Follow the
instructions for submitting comments.
To ensure timely processing of comments, the Commission is no
longer accepting comments submitted by electronic mail (email) except
through www.regulations.gov.
Written Submissions
Submit written submissions in the following way:
Mail/Hand delivery/Courier (for paper, disk, or CD-ROM
submissions), preferably in five copies, to: Office of the Secretary,
U.S. Consumer Product Safety Commission, Room 820, 4330 East West
Highway, Bethesda, MD 20814; telephone (301) 504-7923.
Instructions: All submissions received must include the agency name
and docket number for this proposed rulemaking. All comments received
may be posted without change, including any personal identifiers,
contact information, or other personal information provided, to http://www.regulations.gov. Do not submit confidential business information,
trade secret information, or other sensitive or protected information
electronically.
[[Page 15661]]
Such information should be submitted in writing.
Docket: For access to the docket to read background documents or
comments received, go to http://www.regulations.gov.
FOR FURTHER INFORMATION CONTACT: Joanna Matheson, Ph.D., Project
Manager, Office of Hazard Identification and Reduction, U.S. Consumer
Product Safety Commission, 5 Research Place, Rockville, MD 20850;
telephone (301) 987-2564; [email protected].
SUPPLEMENTARY INFORMATION:
A. Background
The FHSA, 15 U.S.C. 1261-1278, requires appropriate cautionary
labeling on certain hazardous household products to alert consumers to
the potential hazards that a product may present. Among the hazards
addressed by the FHSA are products that are toxic, corrosive,
irritants, flammable, combustible, or strong sensitizers.
Included within the FHSA's definition of ``hazardous substance'' is
``any substance or mixture of substances'' that ``is a strong
sensitizer,'' 15 U.S.C. 1261(f)(1)(iv). Section 2(k) of the FHSA, 15
U.S.C. 1261(k), defines ``strong sensitizer'' as:
A substance which will cause on normal living tissue through an
allergic or photodynamic process a hypersensitivity which becomes
evident on reapplication of the same substance and which is
designated as such by the Commission. Before designating any
substance a strong sensitizer, the Commission, upon consideration of
the frequency of occurrence and severity of the reaction, shall find
that the substance has a significant potential for causing
hypersensitivity.
On August 12, 1961, the Food and Drug Administration (FDA) (which
at that time administered the FHSA), issued regulations under the FHSA
that supplemented the statutory definition of ``strong sensitizer.''
The regulations also provided a list of substances that the FDA had
determined met the statutory definition for ``strong sensitizer.'' The
five substances identified were: (1) Paraphenylenediamine and products
containing it; (2) powdered orris root and products containing it; (3)
epoxy resins systems containing in any concentration ethylenediamine,
diethylenetriamine, and diglycidyl ethers of molecular weight less than
200; (4) formaldehyde and products containing 1 percent or more of
formaldehyde; and (5) oil of bergamot and products containing 2 percent
or more of oil of bergamot. No additional substances have been
determined to be ``strong sensitizers'' by the FDA or the Commission
since promulgation of this regulation.
In 1973, the responsibility for the administration of the FHSA was
transferred to the Commission, and the supplemental definition of
``strong sensitizer'' was published in title 16 of the Code of Federal
Regulations. On May 30, 1984, the Commission revoked the above
supplemental definition of ``strong sensitizer.'' 49 FR 22464. The
Commission concluded at that time that the statutory definition of
``strong sensitizer'' was adequate for any future regulatory
determination that a substance is a strong sensitizer.
On August 14, 1986, the Commission issued a rule supplementing the
definition of ``strong sensitizer'' in the FHSA, 51 FR 29094, which
currently is in effect. 16 CFR 1500.3(c)(5). As recommended by a
Technical Advisory Panel on Allergic Sensitization (TAPAS), the
supplemental definition clarifies how the statutory definition should
be interpreted and explains the factors the Commission will consider in
determining whether a substance is a ``strong sensitizer.'' The
supplemental definition states that an ``allergic'' response is one
that is directed by the immune system, such that a sensitization
reaction could not be caused by an irritant or other nonallergenic
qualities of the substance. The supplemental definition also clarifies
that active sensitizers--substances that produce a sensitivity reaction
solely as the result of a person's first exposure to the substance as
opposed to after reapplication of the same substance--are included
within the class of substances that can be determined to be strong
sensitizers. The supplemental definition did not address strong
sensitizers that cause hypersensitivity by a photodynamic process,
principally because Commission staff was unaware of any household
product subject to the FHSA that would cause significant exposure of
consumers to a photodynamic chemical.
The current supplemental definition makes clear that a sensitivity
reaction could occur after the sensitizer is applied to the body's
tissues by contact, ingestion, or inhalation; that relevant exposure is
not limited to skin contact; and that targets for hypersensitivity
reactions include the skin and other organ systems, such as the
respiratory or gastrointestinal tracts, either alone or in combination.
The supplemental definition states that the minimal severity of the
reaction caused by the substance for purposes of determining whether
the substance is a strong sensitizer is a clinically important allergic
reaction and provides examples of such clinically important reactions.
Whether a substance has a significant potential for causing
hypersensitivity is a relative determination that must be made
separately for each substance under consideration by the Commission.
The supplemental definition sets forth the criteria to be considered in
making this determination. Finally, the supplemental definition
provides the quantitative and qualitative factors that the Commission
should consider in determining that a substance is a ``strong''
sensitizer, such as the frequency of occurrence and range of severity
in normal and susceptible populations and the results of experimental
assays in humans and animals.
Recognizing that the science on sensitization has changed since
promulgation of the supplemental definition in 1986, the CPSC convened
a panel of scientific experts from academia, industry, and the federal
government to examine the available scientific and medical information
concerning sensitizers, and if appropriate, propose revisions to the
supplemental definition of strong sensitizer.
B. Effect of Strong Sensitizer Determination
The Commission is proposing to revise its supplemental definition
of strong sensitizer. Additional Commission action would be needed for
any substance to be designated a strong sensitizer. In order for the
Commission to issue a rule declaring any particular substance (or
product containing that substance) to be a strong sensitizer, it must
engage in notice and comment rulemaking, separate from this rulemaking,
and make the findings specified in 15 U.S.C. 1261(k), i.e., that based
upon consideration of the frequency of occurrence and the severity of
the reaction, the substance has a significant potential for causing
hypersensitivity. However, a determination that a substance is a strong
sensitizer does not automatically trigger a labeling requirement for
products containing that substance. Under the FHSA a substance (or
product containing that substance) that is a hazardous substance
requires appropriate labeling. 15 U.S.C. 1261(p). If manufacturers of
products containing a designated strong sensitizer determine that the
strong sensitizer in their products may cause substantial injury or
illness as a result of reasonably foreseeable handling or use, that
product would be a ``hazardous substance'' as defined under the FHSA,
and therefore would warrant
[[Page 15662]]
appropriate labeling. Alternatively, where there is uncertainty, the
Commission has the option under section 3(a)(1) of the FHSA to
determine through notice and comment rulemaking that a product
containing a strong sensitizer is a ``hazardous substance.'' Hazardous
substances intended or packaged in a form suitable for use in the
household that do not bear the appropriate cautionary labeling would be
considered ``misbranded'' in violation of the FHSA. 15 U.S.C. 1261(p).
Such cautionary labeling would be insufficient, however, if a toy
or other article intended for the use of children is, bears, or
contains a hazardous substance (as that term is defined in section 2(f)
of the FHSA), and the hazardous substance is accessible to a child to
whom the article is entrusted. Under that scenario, the toy or
children's article would be considered a ``banned hazardous substance''
under section 2(q)(1)(A) of the FHSA unless a particular exemption
applies. 15 U.S.C. 1261(q)(1)(A).
C. Proposed Amendment
The proposed amendment to 16 CFR part 1500 clarifies or adds
language to the supplemental definition of ``strong sensitizer'' to
eliminate redundancy, remove certain subjective factors, incorporate
new and anticipated technology, rank the criteria for classification of
strong sensitizers in order of importance, define criteria for
``severity of reaction,'' and indicate that a weight-of-evidence
approach will be used to determine the strength of the sensitizer.
1. Definition of sensitizer. The current definition of sensitizer
in Sec. 1500.3(c)(5) is, ``a substance that will induce an
immunologically-mediated (allergic) response, including allergic
photosensitivity. The allergic reaction will become evident upon
reexposure to the same substance. Occasionally, a sensitizer will
induce and elicit an allergic response on first exposure by virtue of
active sensitization.''
The proposed amendment reflects the traditional definition for
sensitization; sensitization is a multi-stage immune mediated process
which occurs over a period of time. Under the proposed amendment, those
substances that sensitize through atypical mechanisms, rather than by
inducing an obvious ``immunologically-mediated response'' will be
captured by the assessment process. The proposed amendment also
eliminates the last sentence of the current definition based on
concerns that it may be misinterpreted such that substances that cause
an irritant response only \1\ (the response that is noted after the
first exposure to a substance is more frequently an irritant response
and not an allergic response) could be erroneously included in the
category of ``strong sensitizers.'' Typically, allergic responses are
the result of a two-step process: (1) Induction (sensitization) which
requires sufficient or cumulative exposure to induce an immune response
with few or no symptoms and (2) elicitation when an individual who has
been sensitized demonstrates symptoms upon subsequent exposures. The
phrase ``variable period of exposure'' is included in the proposed
amendment to reflect the latency period which is a characteristic in
the development of sensitization.
---------------------------------------------------------------------------
\1\ An ``irritant response'' is a nonimmune mediated response
and one that results from direct injury to the tissue. An irritant
is any agent that is capable of producing cell damage in any
individual if applied for sufficient time and concentration.
---------------------------------------------------------------------------
2. Definition of significant potential for causing hypersentivity.
Currently, 16 CFR 1500.3(c)(5)(iv) provides that '' `significant
potential for causing hypersensitivity' is a relative determination
that must be made separately for each substance. It may be based upon
the chemical or functional properties of the substance, documented
medical evidence of allergic reactions obtained from epidemiological
studies surveys or individual case reports, controlled in vitro or in
vivo experimental assays, or susceptibility profiles in normal or
allergic subjects.''
The proposed revision to this section reiterates the statutory
requirement that before designating any substance a ``strong''
sensitizer, the Commission must find that the substance has significant
potential for causing hypersensitivity. The proposed revision adds
qualifiers for susceptibility profiles--genetics, age, gender, and
atopic status-- to the list of information or data that may be
considered in determining whether a substance has a significant
potential for causing hypersensitivity; and the proposed revision also
replaces the term ``normal'' with ``non-sensitized.'' These
characteristics are well-known modifiers in the development and
exacerbation of allergic responses to chemical sensitizers; and
replacing the term ``normal'' with ``non-sensitized'' reflects more
accurately what would be considered the general control population.
The proposed revision of this section also incorporates a
discussion of the factors to be considered in determining whether a
substance is a ``strong'' sensitizer. The current supplemental
definition of ``strong sensitizer'' contains a separate subsection that
sets forth factors that should be considered in determining the
strength of a sensitizer. (16 CFR 1500.3(c)(5)(ii)). The current
section includes several factors that are subjective rather than
quantitative (i.e., physical discomfort, distress, hardship) and allows
for risk assessment considerations in connection with an analysis that
should only be a hazard characterization step.
The current definition of strong reads:
In determining that a substance is a ``strong'' sensitizer, the
Commission shall consider the available data for a number of
factors. These factors include any and or all of the following (if
available): Quantitative or qualitative risk assessment, frequency
of occurrence and range of severity of reactions in healthy or
susceptible populations, the result of experimental assays in
animals or humans (considering dose-response factors), with human
data taking precedence over animal data, other data on potency or
bioavailability of sensitizers, data on reactions to a cross-
reacting substance or to a chemical that metabolizes or degrades to
form the same or a cross-reacting substance, the threshold of human
sensitivity, epidemiological studies, and other appropriate in vivo
or in vitro test studies.
The proposed amendment eliminates the ``quantitative or qualitative
risk assessment factor'' because the Commission believes this
terminology is a source of confusion in that it places a risk
assessment step within the hazard identification step of the overall
process of determining whether a product containing a strong sensitizer
requires labeling. The proposed amendment makes clear that a weight-of-
the-evidence approach is to be used in determining the strength of a
sensitizer because of the imprecise nature of some of the current
factors and the potential lack of information or data available to
permit useful consideration of certain factors. Rather than allowing an
``any or all'' approach to what factors would be considered by the
Commission in determining whether a sensitizer is strong, the amendment
ranks data sources in order of importance, following the FHSA
preference for human data over animal data; and the amendment takes
into consideration the value and relevance that certain data would
provide in evaluating the potential of a substance to cause
hypersensitivity. For example, the proposed amendment expresses a
preference for general population epidemiological studies over
occupational studies because the degree of sensitization in the
workplace is likely to be greater than that of the general population,
due to greater
[[Page 15663]]
exposure (both in time and concentration) to the sensitizing agent.
The proposed amendment provides that for a substance to be
considered a ``strong'' sensitizer the substance must be found to
produce a ``clinically important reaction,'' which is defined as a
reaction with a significant impact on the quality of life. Examples of
such reactions included in the proposed revision to this section are
substantial physical discomfort or distress, substantial hardship,
functional or structural impairment, or chronic morbidity. The proposed
revision to this section also directs the Commission to consider the
location of the hypersensitivity response, such as the face, hands, and
feet, and the persistence of clinical manifestations in determining
whether the substance produces a ``clinically important reaction.''
The proposed revision to this section adds several factors the
Commission can consider in determining a substance's sensitizing
potential, for which validated methods currently do not exist but are
in development, such as: Quantitative Structure-Activity Relationships
(QSARs), and in silico \2\ data, along with the caveat that using these
techniques would be in addition to consideration of human and animal
data. We expect that in vitro and in silico validated methods will be
available as part of an integrated testing strategy within the next 5
years, and including these components in the amendment ensures that the
definition is compatible with current science. The proposed revision
also includes a definition of ``bioavailability'' (i.e., the dose of
the substance available to interact with a tissue and that tissue's
ability to absorb the substance and the actual penetrating ability of
the substance).
---------------------------------------------------------------------------
\2\ QSARs are mathematical models that relate a quantitative
measure of chemical structure to biological activity. In silico data
is a computational approach using sophisticated computer models for
the determination of a sensitizing potential. Both of these
approaches are evolving methodologies that have not yet been
validated, but are being pursued as testing options that would
reduce the numbers of expensive laboratory and animal experiments
being carried out.
---------------------------------------------------------------------------
3. Definition of Normal Living Tissue. Currently, 16 CFR
1500.3(c)(5)(v) defines normal living tissue as:
the skin and other organ systems, such as the respiratory or
gastrointestinal tract, either singularly or in combination,
following sensitization by contact ingestion or inhalation.
The proposed revision adds a specific reference to mucous
membranes, such as ocular and oral systems, as types of normal living
tissue upon which a substance can cause a hypersensitivity that
warrants a determination that a substance is a ``strong sensitizer.''
4. Definition of Severity of Reaction. The current definition for
severity of reaction at 16 CFR 1500.3(c)(5)(iii)) states that the
minimal severity of a reaction for the purpose of designating a
material as a ``strong sensitizer'' is a clinically important reaction,
and provides examples of the types of illnesses that could satisfy this
criteria, such as physical discomfort, distress, hardship, or
functional or structural impairment.
The proposed amendment eliminates this subsection and incorporates
the factors to be considered in determining whether a substance is a
``strong'' sensitizer into the proposed revised section Significant
potential for causing hypersensitivity.
D. Staff Guidance and Notice of Availability
Commission staff has developed a guidance document that is intended
to clarify the ``strong sensitizer'' definition and assist
manufacturers in understanding how CPSC staff would assess whether a
substance and/or product containing that substance should be considered
a ``strong sensitizer.'' A Notice of Availability is published
elsewhere in this issue of the Federal Register, which provides a link
to the location on the Commission's Web site where the staff guidance
document can be found.
E. Impact on Small Businesses
Under the Regulatory Flexibility Act (RFA), when an agency issues a
proposed rule, it generally must prepare an initial regulatory
flexibility analysis describing the impact the proposed rule is
expected to have on small entities. 5 U.S.C. 603. The RFA does not
require a regulatory flexibility analysis if the head of the agency
certifies that the rule will not have a significant effect on a
substantial number of small entities. Id. 605(b).
The Commission's Directorate for Economic Analysis prepared a
preliminary assessment of the impact of revising the supplemental
definition of ``strong sensitizer.'' That assessment found that there
would be little or no effect on small businesses and other entities
because the proposed amendment, which simply modifies the existing
supplemental definition of ``strong sensitizer,'' will not result in
product modifications to comply; nor will the revised supplemental
definition impose any additional testing or recordkeeping burdens. The
obligation to label a product as a ``strong sensitizer'' and any costs
associated with that obligation will not arise until the Commission has
designated a substance contained in the product as a ``strong
sensitizer,'' which would occur only in connection with a separate
notice and comment rulemaking proceeding. Thereafter, we would assess
the potential small business impact of designating the particular
substance as a strong sensitizer. Moreover, the proposed amendment is
not expected to impose any indirect burden on small businesses or other
entities because it is not expected to lead to any additional
substances being designated as strong sensitizers that would not be so
designated in the absence of the amendment. Based upon the foregoing
assessment, the Commission finds preliminarily that the proposed rule
would not have a significant impact on a substantial number of small
entities.
F. Environmental Considerations
Generally, CPSC rules are considered to ``have little or no
potential for affecting the human environment,'' and environmental
assessments and environmental impact statements are not usually
prepared for these rules (see 16 CFR 1021.5(c)(1)). The Commission does
not expect the proposed rule to have any adverse impact on the
environment under this categorical exclusion.
G. Executive Orders
According to Executive Order 12988 (February 5, 1996), agencies
must state in clear language the preemptive effect, if any, of new
regulations. Section 18 of the FHSA addresses the preemptive effect of
certain rules issued under the FHSA. 15 U.S.C. 1261n. Because this
rulemaking would revise a regulatory definition rather than issue a
labeling or banning requirement, section 18 of the FHSA does not
provide for the proposed rule to have preemptive effect.
H. Paperwork Reduction Act
This rule would not impose any information collection requirements.
Accordingly, this rule is not subject to the Paperwork Reduction Act,
44 U.S.C. 3501-3520.
I. Effective Date
The Administrative Procedure Act generally requires that a
substantive rule be published not less than 30 days before its
effective date, unless the agency finds, for good cause shown, that a
lesser time period is required. 5 U.S.C. 553(d)(3). We propose that the
rule would take effect 30 days after
[[Page 15664]]
publication of a final rule in the Federal Register.
List of Subjects in 16 CFR Part 1500
Consumer protection, Hazardous substances, Imports, Infants and
children, Labeling, Law enforcement, Reporting and recordkeeping
requirements, and Toys.
Accordingly, 16 CFR part 1500 is proposed to be amended as follows:
PART 1500--[AMENDED]
0
1. The authority citation for part 1500 continues to reads as follows:
Authority: 15 U.S.C. 1261-1278.
0
2. In Sec. 1500.3, revise paragraph (c)(5) to read as follows:
Sec. 1500.3 Definitions.
* * * * *
(c) * * *
(5) The definition of strong sensitizer in section 2(k) of the
Federal Hazardous Substances Act (restated in 16 CFR 1500.3(b)(9)) is
supplemented by the following definitions:
(i) Sensitizer. A sensitizer is a substance that is capable of
inducing a state of immunologically mediated hypersensitivity
(including allergic photosensitivity) following a variable period of
exposure to that substance. Hypersensitivity to a substance will become
evident by an allergic reaction elicited upon reexposure to the same
substance.
(ii) Significant potential for causing hypersensitivity. Before
designating any substance a ``strong sensitizer,'' the Commission shall
find that the substance has significant potential for causing
hypersensitivity. Significant potential for causing hypersensitivity is
a relative determination that must be made separately for each
substance. It may be based on chemical or functional properties of the
substance; documented medical evidence of allergic reactions upon
subsequent exposure to the same substance obtained from epidemiological
surveys or individual case reports; controlled in vitro or in vivo
experimental studies; and susceptibility profiles (e.g., genetics, age,
gender, atopic status) in non-sensitized or allergic subjects.
(A) In determining whether a substance is a ``strong'' sensitizer,
the Commission shall consider the available data for a number of
factors, following a weight-of-evidence approach. The following factors
(if available), ranked in descending order of importance, should be
considered: well-conducted clinical and diagnostic studies,
epidemiological studies, with a preference for general population
studies over occupational studies, well-conducted animal studies, well-
conducted in vitro test studies, cross-reactivity data, and case
histories. Criteria for a ``well-conducted'' study would include
validated outcomes, relevant dosing and route of administration, and
use of appropriate controls. Studies should be carried out according to
national and/or international test guidelines and according to good
laboratory practice (GLP), compliance with good clinical practice
(GCP), and good epidemiological practice (GEP).
(B) Before the Commission designates any substance a ``strong''
sensitizer, frequency of occurrence and range of severity of reactions
in exposed subpopulations having average or high susceptibility will be
considered. The minimal severity of a reaction for the purpose of
designating a material a ``strong sensitizer'' is a clinically
important reaction. A clinically important reaction would be considered
one with loss of function and significant impact on quality of life.
Consideration should be given to the location of the hypersensitivity
response, such as the face, hands, and feet and persistence of clinical
manifestations. For example, strong sensitizers may produce substantial
illness, including any or all of the following: substantial physical
discomfort and distress, substantial hardship, functional or structural
impairment, chronic morbidity.
(C) Additional consideration may be given to Quantitative
Structure-Activity Relationships (QSARs), in silico data, specific
human sensitization threshold values, and other data on potency and
sensitizer bioavailability, if data are available and methods are
validated. Bioavailability is the dose of the allergen available to
interact with a tissue. It is a reflection of how well the skin or
another organ can absorb the allergen and the actual penetrating
ability of the allergen, including factors such as size and composition
of the chemical.
(iii) Normal living tissue. The allergic hypersensitivity reaction
occurs in normal living tissues, including the skin, mucous membranes
(e.g., ocular, oral), and other organ systems, such as the respiratory
tract, gastrointestinal tract, or either singularly or in combination,
following sensitization by contact, ingestion, or inhalation.
* * * * *
Dated: March 7, 2013.
Todd A. Stevenson,
Secretary, U.S. Consumer Product Safety Commission.
[FR Doc. 2013-05577 Filed 3-11-13; 8:45 am]
BILLING CODE 6355-01-P